Only a small population (25–30%) of human peripheral blood B lymphocytes expresses large sialoglycoprotein (LSGP) (CD43). However, in the presence of autologous T cells and pokeweed mitogen (PWM) a majority (50–90%) of the immunoglobulin-producing cells (cÍg+ cells) that develop from these B cells express CD43 is detected with anti-CD43 monoclonal antibodies (MoAb) B1B6, and the proportion of CD43+cIg+ cells increases with time of culture. Furthermore, a relatively larger proportion (60–80%) of the IgG-producing cIg+ cells are CD43+ compared with IgM-containing cIg+ cells (30–50%). In human tonsils, signficantly more CD43+ cells (35%) are found in the in vivo-activated fraction of B cells than in the fraction of resting B cells (5%). A majority of the cIg+ cells that develop from the resting or the in vivo-activated tonsillar B cells in a PWM-induced B-cell differentiation system are CD43+ (80–100%). Furthermore, tonsillar B cells depleted of CD43+ cells give rise to cIg+ cells, of which the majority are CD43+, and the proportion of such cells increases with time of culture (60–90%). Taken together, these results indicate that LSGP belongs to a group of B-cell membrane molecules that are induced and upregulated upon activation and differentiation.